Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells.

Urea and hypertonicity increase expression of heme oxygenase-1 in murine renal medullary cells.
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尿素和高渗会增加小鼠肾髓质细胞中血红素加氧酶-1 的表达。

DOI:
10.1152/ajprenal.0358.2000
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发表时间:
2001
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Cohen,DM
Cohen,DM
中科院分区:
--
文献类型:
--
作者:
Tian,W;Bonkovsky,HL;Shibahara,S;Cohen,DM

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First Published August 15, 2001; 10.1152/ajprenal. 00358.2001.—Epithelial cells derived from the mammalian kidney medulla are responsive to urea at the levels of signal transduction and gene regulation. Hybridization of RNA harvested from control- and urea-treated murine inner medullary collecting duct (mIMCD3) cells with a cDNA expression array encoding stress-responsive genes suggested that heme oxygenase (HO)-1 mRNA was upregulated by urea. RNase protection assay confirmed this upregulation; hypertonicity also increased HO-1 mRNA expression but neither hypertonic NaCl nor urea were effective in the nonrenal 3T3 cell line. The effect on HO-1 expression appeared to be transcriptionally mediated on the basis of mRNA half-life studies and reporter gene analyses using the promoters of both human and chicken HO-1. Although urea signaling resembles that of heavy metal signaling in other contexts, the effect of urea on HO-1 transcription was independent of the cadmium response element in this promoter. Urea-inducible HO-1 expression was sensitive to antioxidants but not to scavengers of nitric oxide. Urea also upregulated HO-1 protein expression and pharmacological inhibition of HO-1 action with zinc protoporphyrin-sensitized mIMCD3 cells to the adverse effects of hypertonicity but not to urea. Coupled with the prior observation of others that HO-1 expression increases along the renal corticomedullary gradient, these data suggest that HO-1 expression may comprise an element of the adaptive response to hypertonicity and/or urea in renal epithelial cells.
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